Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation
Article first published online: 8 MAR 2012
© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society
Journal of Pharmacy and Pharmacology
Themed Issue: Inhalation Pharmaceutics – Current Technologies and Approaches to Respiratory Drug Delivery. Guest Editors: Paul M. Young and Daniela Traini
Volume 64, Issue 9, pages 1275–1290, September 2012
How to Cite
NíÓgáin, O., Tajber, L., Corrigan, O. I. and Healy, A. M. (2012), Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation. Journal of Pharmacy and Pharmacology, 64: 1275–1290. doi: 10.1111/j.2042-7158.2012.01488.x
- Issue published online: 6 AUG 2012
- Article first published online: 8 MAR 2012
- Received July 29, 2011; Accepted January 23, 2012
- nanoporous/nanoparticulate microparticles;
Objectives The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation.
Methods Trypsin was spray-dried with raffinose from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed.
Key findings The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs.
Conclusions NPMPs of trypsin : excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin.